System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Ppublish 4 citations

PubMed: 39621903 DOI: 10.1073/pnas.2415119121

Transcriptional reprogramming primes CD8+ T cells toward exhaustion in Myalgic encephalomyelitis/chronic fatigue syndrome.

Proc Natl Acad Sci U S A 121(50):e2415119121

Authors: David S Iu, Jessica Maya, Luyen T Vu, Elizabeth A Fogarty, Adrian J McNairn, Faraz Ahmed, Carl J Franconi, Paul R Munn, Jennifer K Grenier, Maureen R Hanson, Andrew Grimson

Affiliations

  • Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853.
  • Genomics Innovation Hub and TREx Facility, Cornell University, Ithaca, NY 14853.

Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME) is a severe, debilitating disease, with substantial evidence pointing to immune dysregulation as a key contributor to pathophysiology. To characterize the gene regulatory state underlying T cell dysregulation in ME, we performed multiomic analysis across T cell subsets by integrating single-cell RNA-seq, RNA-seq, and ATAC-seq and further analyzed CD8+ T cell subpopulations following symptom provocation. Specific subsets of CD8+ T cells, as well as certain innate T cells, displayed the most pronounced dysregulation in ME. We observed upregulation of key transcription factors associated with T cell exhaustion in CD8+ T cell effector memory subsets, as well as an altered chromatin landscape and metabolic reprogramming consistent with an exhausted immune cell state. To validate these observations, we analyzed expression of exhaustion markers using flow cytometry, detecting a higher frequency of exhaustion-associated factors. Together, these data identify T cell exhaustion as a component of ME, a finding which may provide a basis for future therapies, such as checkpoint blockade, metabolic interventions, or drugs that target chronic viral infections.

MeSH

Cells, Flow Cytometry, Encephalomyelitis, Fatigue Syndrome, Chronic, Fatigue

Cited by